The FDA has approved AstraZeneca's Imfinzi (durvalumab) for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. This approval marks a significant advancement in the treatment of this aggressive form of lung cancer, which has seen limited progress in recent decades. The decision was based on the positive results from the Phase III ADRIATIC trial, a randomized, double-blind, placebo-controlled study involving 730 patients. The trial demonstrated a substantial improvement in overall survival (OS) and progression-free survival (PFS) with Imfinzi compared to placebo.
ADRIATIC Trial Results
The ADRIATIC trial, a multi-center, international study, evaluated Imfinzi monotherapy versus placebo in patients with LS-SCLC who had not progressed after concurrent chemoradiation therapy (cCRT). Key findings from the trial include:
- A 27% reduction in the risk of death with Imfinzi compared to placebo (HR 0.73; 95% CI: 0.57-0.93; p=0.0104).
- Median overall survival (OS) of 55.9 months for Imfinzi versus 33.4 months for placebo.
- An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% for placebo.
- A 24% reduction in the risk of disease progression or death with Imfinzi versus placebo (HR 0.76; 95% CI: 0.61-0.95; p=0.0161).
- Median progression-free survival (PFS) of 16.6 months for Imfinzi versus 9.2 months for placebo.
These results highlight the potential of Imfinzi to transform the treatment landscape for LS-SCLC, offering a new standard of care for patients who have historically faced a poor prognosis. Suresh Senan, PhD, Professor of Clinical Experimental Radiotherapy at the Amsterdam University Medical Centers, noted that the ADRIATIC trial showed 57% of patients were still alive at three years after being treated with durvalumab, which underscores the practice-changing potential of this medicine in this setting.
Impact on Clinical Practice
LS-SCLC accounts for approximately 30% of SCLC diagnoses and is typically confined to one lung or one side of the chest. Despite initial responses to standard-of-care chemotherapy and radiotherapy, the disease often recurs and progresses rapidly. The prognosis for LS-SCLC is particularly poor, with only 15-30% of patients surviving five years after diagnosis. The approval of Imfinzi provides a much-needed treatment option for these patients, offering the potential for improved survival outcomes.
Dave Fredrickson, Executive Vice President of AstraZeneca's Oncology Business Unit, emphasized that this approval marks a breakthrough for patients with limited-stage small cell lung cancer, allowing them to receive immunotherapy for the first time. He added that the ADRIATIC trial showed an improvement in median overall survival of 22.5 months, setting a new benchmark.
Dosing and Administration
The recommended dose of durvalumab is 1,500mg every four weeks for patients weighing 30kg or more, and 20mg/kg every four weeks for those weighing less than 30kg. Treatment is advised until disease progression, unacceptable toxicity, or for a maximum of 24 months.
Mechanism of Action
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the programmed death-ligand 1 (PD-L1) protein, blocking its interaction with PD-1 and CD80 proteins. This mechanism counters the tumor's immune-evading tactics and releases the inhibition of immune responses, allowing the body's immune system to attack the cancer cells.
Ongoing Regulatory Reviews
In addition to the US approval, Imfinzi is also approved in Switzerland for the treatment of LS-SCLC based on the ADRIATIC results. Regulatory applications are currently under review in the EU, Japan, and several other countries, potentially expanding access to this important therapy for patients worldwide.
